The long-term goal of this project is the development of a multivalent anti-S. aureus vaccine/cocktail of anti-S. aureus mAbs that will be composed of several toxoid antigens or mAbs against the most important S. aureus toxins, respectively. In addition, mAbs against PSMalpha3 will be an indispensable tool for our planned high-throughput screen for agents inhibiting PSM secretion. Specifically, we plan to: Test all PSMalpha3 derivatives for their immunogenic potential Test all PSMalpha3 derivatives (active vaccination) in animal protection assays (using skin, bacteremia, and pneumonia infection models) Produce mAbs against PSMalpha3 and a selection of PSMalpha3 derivatives Test the efficacy of those mAbs in protecting from S. aureus-induced disease in various infection models (skin, bacteremia, pneumonia) In the current FY, we have completed production of polyclonal Abs and mAbs against PSMalpha3.